title: Protein kinase inhibitor as a potential candidate for epilepsy treatment.
abstract: OBJECTIVE
  Effects of the "VID-82925" kinase inhibitor molecule were investigated both during the developing phase as well as during the stable phase of the focus with spontaneous recurrent seizures using the 4-AP-induced in vivo epilepsy model in anesthetized rats.
  
  
  METHODS
  In electrophysiologic experiments, VID-82925 (0.85 mg/kg) was injected intravenously either before the induction (pretreatment) or after the development of the stable focus (treatment). Reference drugs carbamazepine (4.8 mg/kg) and levetiracetam (50 mg/kg) were employed using the same experimental paradigm. The antiepileptic effect of VID-82925 was also compared to those of the broad-spectrum gap junction channel blocker carbenoxolone (10 mm).
  
  
  RESULTS
  Pretreatment with VID-82925 revealed an antiepileptogenic effect as it suppressed significantly the manifestation of the epileptiform activity not only during the developing phase, but also for a considerable long period during the stable phase of the focus. The current data do not allow us to differentiate an antiictal treatment effect from an antiepileptogenic effect of the compound during the stable phase of the focus. Treatment with VID-82925 was also effective against ictogenesis during the stable phase of the focus. Pretreatment with levetiracetam failed to exert any antiepileptogenic effect. The antiepileptic effects of VID-82925 and of the reference drugs on the epileptiform activity of the stable focus were comparable in intensity; however, the effect of VID-82925 was 2-3 times longer. The effects of VID-82925 and of carbenoxolone overlapped one another to some extent, suggesting that VID-82925 may exert its effects at least partially through blocking of gap junctional communication.
  
  
  CONCLUSIONS
  Our results indicate that inhibition of protein kinases may also provide an effective strategy for the development of a drug that is not only antiepileptic but also depresses the course of epileptogenesis.
authors.affiliation: Department of Comparative Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Gajda
authors.forename: Rita
authors.initials: R
authors.lastname: Török
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Horváth
authors.forename: Csaba
authors.initials: C
authors.lastname: Szántai-Kis
authors.forename: László
authors.initials: L
authors.lastname: Orfi
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.forename: Magdolna
authors.initials: M
authors.lastname: Szente
mesh_terms: D015761:4-Aminopyridine; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D004569:Electroencephalography / Q000187:drug effects; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology; D011292:Premedication; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012815:Signal Processing, Computer-Assisted
chemical_list: D000927:Anticonvulsants; D047428:Protein Kinase Inhibitors; D002220:Carbamazepine; D000077287:Levetiracetam; D015761:4-Aminopyridine; D002229:Carbenoxolone; D010889:Piracetam